DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Thymic Squamous Cell Carcinoma — screening already-approved drugs against its 43-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleThymic Squamous Cell Carcinoma maps to a 43-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for thymic squamous cell carcinoma is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
fibroblast growth factor receptor 4 (FGFR4) — FGFR4 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 1~{r}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8KH8 · 1.49 Å · ligand 1-[4-[(1~{R})-1-[3,5-bis(chloranyl)pyridin-4-yl]ethoxy]-5-cyano-pyridin-2-yl]-3-[6-methanoyl-5-[(4-methyl-2-oxidanylidene-piperazin-1-yl)methyl]-3-(2-morpholin-4-ylethoxy)pyridin-2-yl]urea (VVW). Experimental structure, not a prediction.
What the evidence adds up to
Thymic squamous cell carcinoma is a rare and aggressive neoplasm. In a series of ten patients with resected thymic carcinoma (nine squamous cell, one mixed), the five-year and ten-year survival rates were 78.7% and 52.5% respectively; eight of the ten patients underwent complete resection, and all received postoperative radiotherapy of 20–50 Gy. A larger retrospective study of 106 completely resected squamous thymic carcinoma patients reported a five-year overall survival of 68.4% and a five-year freedom from recurrence of 52.8%; the median freedom from relapse was 26 months. In that study, Masaoka stage was the only prognostic factor for both overall survival and freedom from recurrence, and adjuvant chemotherapy was associated with improved freedom from recurrence in stage II and stage III disease, and with a lower proportion of metastasis in those stages.
A separate analysis of 114 patients with stage III squamous thymic carcinoma found a five-year overall survival of 69.7%. Complete resection was the most important prognostic factor: five-year overall survival was 72.5% for the complete resection group, 31.4% for the non-complete resection group, and 41.5% for the non-surgery group. In this stage III cohort, neither adjuvant chemotherapy nor adjuvant radiotherapy demonstrated an overall survival benefit, and patients who received inductive therapy had poorer overall survival than those who did not. Concurrent chemo-radiotherapy showed no survival benefit for progression-free or overall survival.
A small multimodality study of seven patients used neoadjuvant chemotherapy with cisplatin, epidoxorubicin and etoposide, followed by surgery and postoperative radiotherapy. All seven patients responded to chemotherapy (one completely). Surgical resection was complete in four cases. At the time of reporting, three patients were alive and well at 62–136 months, two were alive with relapse at 16 and 85 months, one died from another cause at 86 months, and one died from local relapse and lung metastases at 18 months. The authors described the results as preliminary and called for a multicentre trial with sufficient numbers.
One case report described a 66-year-old man with thymic small cell carcinoma that transformed into squamous cell carcinoma after third-line treatment. He received anlotinib as fourth-line therapy and had a progression-free survival of 25 months and an overall survival of 10 years. No controlled data exist for anlotinib in this setting. A cautionary note from 2018 states that the rarity of thymic carcinoma has prevented large randomised trials, and that all current data come from phase II trials and retrospective studies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
European Journal of Cardio-Thoracic Surgery · 2001 · 76 citations · open access
The multimodality treatment of thymic carcinoma
AbstractOBJECTIVES: Thymic carcinoma is a rare neoplasm more invasive and with a poorer prognosis than ordinary thymoma. Complete curative resection is sometimes not possible, but good response rates to chemotherapy are reported in literature. We report our experience with seven cases of thymic carcinoma, who took part to a multimodality treatment including neoadjuvant chemotherapy, surgery and post-operative radiotherapy in our center. METHODS: Since June 1989, seven previously untreated patients were enrolled. The primary chemotherapy consisted of three courses of cisplatin (P; 75 mg/m(2) i.v., day 1), epidoxorubicin (E; 100 mg/m(2) i.v., day 1) and etoposide (VP16; 120 mg/m(2) i.v., days 1, 3 and 5), every 3 weeks. Surgery was performed following complete hematological recovery. After surgery, all patients underwent radiation therapy to the tumor areas, operatively marked with clips, at doses of 45 (complete resection) or 60 Gy (incomplete resection). RESULTS: The pre-operative diagnosis of thymic carcinoma was performed in four cases by a mediastinotomy, and in the remaining cases, by an ultrasound-guided (n=2) or a computed tompography-guided (n=1) fine needle aspiration. All patients responded (one completely) to the chemotherapy regimen. Surgical resection was complete in four cases (histological examination negative in one case). Three patients are still alive and well (62-136 months from the diagnosis), two are alive with relapse at 16 and 85 months, one patient died at 86 months from another cause, and one patient died at 18 months from local relapse and lung metastases. CONCLUSIONS: A pre-operative shrinkage of the thymic carcinoma by means of neoadjuvant multi-drug chemotherapy may improve the resectability, and therefore, the survival rate. Our experience, although preliminary, is encouraging and merits additional study in a multicenter trial with a sufficient number of patients to draw definitive conclusions.
Cancer Management and Research · 2022 · 5 citations · open access
Transformation from Small Cell to Squamous Cell Carcinoma in a Thymic Carcinoma Patient with a Durable Response to Anlotinib: A Case Report
AbstractThe most common pathologic type of thymic carcinoma (TC) is squamous cell carcinoma (SCC). Small cell carcinoma is relatively rare, accounting for approximately 2% to 5% of all thymic tumors. Histologic transformation of TC has not yet been reported. Available treatments for TC patients who progress after first-line therapy are limited, which contributes to their poor prognosis. We reported an extraordinary case of a 66-year-old man who was diagnosed with thymic small cell carcinoma that transformed into SCC after third-line treatment. Surprisingly, the patient had a progression-free survival (PFS) of 25 months and an overall survival (OS) of 10 years on anlotinib as fourth-line therapy. The tolerance was well. Thus, anlotinib may be a safe and promising treatment for TC patients, especially those who undergo histologic transformation.
The Journal of the Japanese Association for Chest Surgery · 2003 · 2 citations · open access
A clinical study of thymic carcinomas
AbstractWe reviewed ten patients with resected thymic carcinoma. The mean age was 55.0 years, ranging from 36 to 71 years, with five males and five females. The histological types were squamous cell carcinoma in 9 cases, and squamous cell carcinoma combined with small cell carcinoma in one case. One of the 10 patients was in stage I, 7 were in stage III, one was in stage IVa, and one was in stage IVb. Eight of the ten patients underwent complete resection, and induction chemotherapy was performed in one of the 8 cases, while induction chemoradiotherapy was performed in two of the 8 cases. Postoperative radiotherapy was performed in all cases (20-50Gy). In recurrence cases, operation was positively performed for resectable cases. The five-year and ten-year survival rates were 78.7%, 52.5%, respectively. We expect that patients with thymic carcinoma can be cured completely or survive for long periods with multimodal therapy and resection of recurrences.
Pembrolizumab in patients with thymic carcinoma: a cautionary tale
AbstractThe development of novel treatment options for advanced-stage thymic neoplasms remains a challenge. The rarity of this disease has precluded the conduct of large randomized controlled trials and all current data stem from phase II clinical trials and retrospective cohort studies. Thymic carcinomas comprise a small subset of thymic epithelial neoplasms and despite the fact that they behave more aggressively and have a worse prognosis than thymomas, they are either analyzed in combination with thymomas or excluded from clinical trials altogether (1).
AbstractBackground: To evaluate the efficacy of adjuvant chemotherapy for completely resected squamous thymic carcinoma. Methods: Between 2009 and 2015, 196 consecutive patients who were diagnosed with squamous thymic carcinoma were collected. Patients of non-surgery, non-complete resection, neo-adjuvant therapy and those of Masaoka-Iva stage were excluded from the study. Clinical data were reviewed. Outcome measures included overall (OS) and freedom from recurrence (FFR). In all, 106 patients of completely resection were enrolled in this retrospective study. Results: The median age was 56 years (range, 25–80 years). The clinical stage distribution according to the Masaoka system of I, II, III and IVb were 2 (2%), 37 (35%), 52 (49%), 15 (14%). Sixty-seven patients received adjuvant chemotherapy and 97 patients received adjuvant radiotherapy. With a median follow-up period of 56 months (range, 25–116 months), 31 patients died from disease. Forty-eight patients developed metastases, with a higher proportion (80%) in Masaoka stage IVb. The most common metastatic sites were lung (n=19). Two patients developed mediastinal relapse. The median freedom from relapse (FFR) was 26 months. Five-year overall survival (OS) and FFR were 68.4% and 52.8%. Masaoka stage was the only prognostic factor both for OS and FFR. Adjuvant chemotherapy remained associated with improved FFR in stage III of 52 patients (P=0.017) and a trend with OS (P=0.059). FFR in patients of stage II receiving four cycles of adjuvant chemotherapy was superior to that in patients not receiving adjuvant chemotherapy (P=0.041). Adjuvant chemotherapy for stage II and III squamous thymic carcinoma was statistically significantly associated with lower proportion of metastasis (P=0.038). Conclusions: Completely resected squamous thymic carcinoma showed a relative good long-term survival. Advanced Masaoka stage was associated with shorter survival, especially for stage IVb. Adjuvant chemotherapy demonstrated improved outcomes in Masaoka stage II and III.
AB023. PS01.05. Clinical outcomes for stage-III thymic squamous carcinoma
AbstractBackground: The objective of this study was to retrospectively evaluate the clinical survival of stage-III squamous thymic carcinoma. Methods: From January 2008 to December 2015, 114 patients of stage-III squamous thymic carcinoma treated in our hospital were enrolled. There were 70 male and 44 female, mean age of 54 years (range, 14–77 years). Ninety-seven patients underwent surgical resection, while seventy-three patients were completely resected. Twenty patients received inductive therapy, including inductive sequential chemo-radiotherapy (10 patients) and inductive concurrent chemo-radiotherapy (10 patients). In 73 patients who were completely resected, 45 patents were of T2 stage. Forty patients received adjuvant chemotherapy and sixty-five patients received adjuvant radiotherapy. Results: The median follow-up period from patients’ first time diagnose was 48 months (18–108 months). Five-year overall survival (OS) rate was 69.7%, respectively. Five-year OS for the complete resection group, non-complete resection group and non-surgery group were 72.5%, 31.4% and 41.5% (P=0.00). Five-year FFR was 46.3% for the complete resection group. Neither adjuvant chemotherapy (P=0.987) nor adjuvant radiotherapy (P=0.095) demonstrated OS benefit. Five-year FFR and OS for the inductive group was 29.6% and 46.7% vs. 51.8% and 77.7% for the non-inductive group (P=0.221, P=0.033). According to the TNM staging systems for thymic tumor, invading pericardium (T2) showed good OS (P=0.044) in the R0 resection group. Five-year OS and PFS was 31.4% and 13.9% for non-complete resection group vs. 41.5% and 0 for non-surgery group (P=0.443, P=0.355). Concurrent chemo-radiotherapy did not show survival benefit neither for PFS nor OS (P=0.427, P=0.912). Conclusions: Complete resection appeared to be the most important prognostic fact for stage III squamous thymic carcinoma. Patients treated with inductive therapy had poorer OS than those patients who did not. Tumor invading pericardium (T2) showed good OS in the R0 resection group.
Oncology Reviews · 2011 · 0 citations · open access
Chemotherapy in the treatment of thymic tumors
AbstractThymic tumors, including thymoma and thymic carcinoma, are mainly treated with surgical resection. The majority of patients with thymic tumors present with early stage and are cured with surgical excision with or without post-operative radiation. For the patients who present with unresectable stage III or IV disease, or for the patients who experience recurrence, chemotherapy can play a significant role in ensuring long-term survival and offering palliation. Thymic tumors are chemo-sensitive with optimal responses achieved with cisplatin-based combinations. A multimodality approach including chemotherapy and post-operative radiation can improve complete resection rates and longterm outcomes in locally advanced tumors. Patients with disseminated thymic tumors can have significant disease response and symptom palliation when treated with chemotherapy. Durable responses can be obtained both in metastatic and recurrent settings. Second-line treatments are available and novel therapies are currently being explored. This review provides an update of available evidence about the treatment of thymic tumors with chemotherapy.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
